Variant 10-19450384-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001142308.3(MALRD1):c.4923G>C(p.Leu1641=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00559 in 1,550,220 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 34 hom. )

Consequence

MALRD1
NM_001142308.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.17

Variant links:

Genes affected

MALRD1 (HGNC:24331): (MAM and LDL receptor class A domain containing 1) This gene encodes a conserved protein that features multiple MAM (meprin-A5-protein tyrosine phosphatase mu) and LDLR A2 (low density lipoprotein receptor A2) domains. Expression of this gene is enriched in the small intestine and is upregulated during differentiation of a human cell line that exhibits properties of intestinal epithelial cells. The encoded protein has been shown to modulate production of FGF19 in a human intestinal cell line and may regulate bile acid metabolism in the liver. A synergistic interaction between an allele of this gene and the APOE E4 allele is associated with an elevated risk of Alzheimer's disease in human patients. [provided by RefSeq, Jul 2017]

MALRD1 links:

LOC102724082 (HGNC:):

LOC102724082 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 10-19450384-G-C is Benign according to our data. Variant chr10-19450384-G-C is described in ClinVar as [Benign]. Clinvar id is 785880.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.17 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MALRD1	NM_001142308.3 linkuse as main transcript	c.4923G>C	p.Leu1641=	synonymous_variant	29/40	ENST00000454679.7	NP_001135780.2
LOC102724082	XR_007062079.1 linkuse as main transcript	n.167+6191C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MALRD1	ENST00000454679.7 linkuse as main transcript	c.4923G>C	p.Leu1641=	synonymous_variant	29/40	1	NM_001142308.3	ENSP00000412763	P1
MALRD1	ENST00000377266.7 linkuse as main transcript	c.2953-38576G>C		intron_variant		5		ENSP00000366477

Frequencies

GnomAD3 genomes

AF:

0.00497

AC:

756

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00524

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00710

Gnomad OTH

AF:

0.00863

GnomAD3 exomes

AF:

0.00458

AC:

686

AN:

149662

Hom.:

AF XY:

0.00460

AC XY:

370

AN XY:

80422

show subpopulations

Gnomad AFR exome

AF:

0.000875

Gnomad AMR exome

AF:

0.00199

Gnomad ASJ exome

AF:

0.00322

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00311

Gnomad FIN exome

AF:

0.00933

Gnomad NFE exome

AF:

0.00639

Gnomad OTH exome

AF:

0.00531

GnomAD4 exome

AF:

0.00565

AC:

7902

AN:

1397936

Hom.:

Cov.:

AF XY:

0.00557

AC XY:

3843

AN XY:

689468

show subpopulations

Gnomad4 AFR exome

AF:

0.000855

Gnomad4 AMR exome

AF:

0.00213

Gnomad4 ASJ exome

AF:

0.00429

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00283

Gnomad4 FIN exome

AF:

0.00942

Gnomad4 NFE exome

AF:

0.00622

Gnomad4 OTH exome

AF:

0.00502

GnomAD4 genome

AF:

0.00496

AC:

756

AN:

152284

Hom.:

Cov.:

AF XY:

0.00543

AC XY:

404

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000987

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0106

Gnomad4 NFE

AF:

0.00710

Gnomad4 OTH

AF:

0.00854

Alfa

AF:

0.00488

Hom.:

Bravo

AF:

0.00418

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.26

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over